Lecture 9: suspensions Flashcards
What are the uses of suspensions?
- For patients who cannot swallow tablets or capsules
- There is no suitable
solvent available to dissolve a drug - To prevent the degradation of the drugs in aqueous environment
- To mask the taste of drugs
- To control the release of drugs
- A high concentration of the drugs can be incorporated into the suspension products
What do the values of logP indicate about a drug?
- Negative logP = more hydrophilic
- Positive logP = more lipophilic
What are the different routes of administration of suspensions?
- Oral
- Topical
- Injectable
What are the desirable properties of suspensions?
- Particles of uniform size and small enough such that they settle slowly
- If they sediment, they , should readily redisperse upon gentle shaking of the container
- The viscosity should be such that it does’nt interfere with pouring and redispersion
- Redispersal should produce uniform dose for administration
- The suspension should be chemically and physically stable
- The drug substance must not change its polymorphic form during
storage - The final formulation should be pleasing to the patient
- It should be safe, effective, stable and pharmaceutically elegant
What are the disadvantages of suspensions?
- Dose uniformity isnt as good as a tablet/capsule
- Sedimentation and cake formation
- Liquid products are bulky
- Difficult to form an effective suspension
- Adhesion of suspension particles to the container walls
What is aggregation, coagulation and flocculation?
- Aggregation is a general term signifying the collection of particles into groups.
- Coagulation signifies that the particles are closely aggregated and difficult to redisperse.
- In flocculation, the aggregates have an open
structure in which the particles remain a small distance apart from one another
What is the state of the particles at the primary minimum, and is this an optimal state for formulating a suspension?
At short distances, VT = -ve i.e., (VA»VR)
Any movement of the particle will bring the particle closer
As the particles undergo sedimentation, they form close packed structures with smaller particles filling the voids between larger one.
Particles in “primary minimum” show a high degree of attraction
and form hard cake and is, therefore, undesirable for
pharmaceutical suspensions
What is the state of the particles at the primary maximum, and is this an optimal state for formulating a suspension?
At intermediate distances VT = Positive (VR»VA) and the double layer repulsion is dominant and forms
primary maximum
Particles in this zone are separated or “deflocculated” if the kinetic energy (kbT) of the particles is less than VT
If kbT» VT, with time the particles undergo sedimentation
Larger particles forms close packed arrangement with smaller particles, therefore, formulating a suspension in this zone is risky
What is the state of the particles at the secondary minimum, and is this an optimal state for formulating a suspension?
- At long distances, the fall-off in repulsive energy with distance is more than that of attractive energy, therefore, VT = less -ve i.e., (VA>VR)
- This allows the formation of flocs at a longer distance of separation.
- Particles in this zone exists as loose aggregates or floccules
- Coalescence and coagulation is minimum and, therefore this is a desirable strategy for preparing a suspension
- In addition, the energy barrier to resuspend the particle is lower and a slight shaking is enough to break the flocks. This is known as controlled flocculation.
How does the addition of non ionic surfactant stabilise a lyophobic colloid?
- It prevents the particles from coming close to each other and reaching the primary minimum
- The side chains of the surfactant are covered by water molecules: for the particles to come very close to each other and form aggregates, you have to remove all these water molecules from the interface which isn’t thermodynamically possible.
- The energy barrier to reach the primary minimum has increased
- This steric effect doesn’t come into effect until the distance between the 2 particles = 2 x the length of the side chains
Can a deflocculated and a flocculated suspension form a hard cake?
Yes for deflocculated
No for flocculated
What is the difference between a flocculated and deflocculated suspension?
- In a flocculated suspension, the particles exist as loose aggregates, whereas in a deflocculated suspension, the particles exist as
separate entities - The velocity of sedimentation is rapid in a flocculated suspension and slow in a deflocculated suspension
- In a flocculated suspension, there is a distinct boundary between sediment and supernatant, whereas in a deflocculated suspension, there is no distinct boundary
between sediment and supernatant - A flocculated suspension is clear while a deflocculated suspension is turbid
- A flocculated suspension is unsightly while a deflocculated suspension is pleasing to look at
- In a flocculated suspension the sediments are loosely packed whereas in a deflocculated suspension the sediments get densely packed to form a hard cake
- The sediments in a flocculated suspension are easily dispersed by shaking while the sediments in a deflocculated suspension are hard to redisperse
Why does high temperature promote the formation of flocculates in sterically hindered suspensions?
Temperature increases the Brownian motion and increases the likelihood that the particles will come into close contact with each other causing coalescence.
How does viscosity affect Brownian motion?
Increasing the viscosity of the medium decreases the Brownian movement
What is the purpose of adding wetting agents?
- To reduce the interfacial tension between the particle surface and dispersion medium
- Improving the flow and increasing the homogeneity of the drug
particles
